RECRUITING

A Phase 1 Trial Evaluating the Long-term Safety and Tolerability of Imatinib for the Treatment of Lymphangioleiomyomatosis (LAM)

Description

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that appears to behave like a slowly growing cancer. Since clinical progression is very slow, new blood tests have been used to speed the time required to find safe and effective medications. A large National Institute of Health study called MILES showed that sirolimus (also known as Rapamycin) improved lung function in individuals with LAM. Since most individuals with LAM and impaired lung function are now on sirolimus, future studies may prove more difficult. Laboratory studies suggested that Imatinib mesylate (imatinib), an FDA-approved drug for leukemia, initiates LAM cell death. A pilot trial with imatinib titled "Imatinib Mesylate for the treatment of Lymphangioleiomyomatosis" - (LAMP-1) was funded by the Department of Defense in 2016, and documented (1) the safety of use of tyrosine kinase inhibitors in patients with LAM; (2) the safety of concurrent use of tyrosine kinase and mTOR inhibitors; and, (3) short term variability in vascular endothelial growth factor D (VEGF-D) - a LAM biomarker, as a response to therapies. Due to the short-term LAMP-1 trial, LAMP-2 will be a longer-term 6-month clinical study evaluating the safety and tolerability of imatinib in patients with LAM. Patients that participate in the trial will come in for 5 office visits and check-up phone calls every 2 weeks over the course of 6 months.

Study Overview

Study Details

Study overview

Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that appears to behave like a slowly growing cancer. Since clinical progression is very slow, new blood tests have been used to speed the time required to find safe and effective medications. A large National Institute of Health study called MILES showed that sirolimus (also known as Rapamycin) improved lung function in individuals with LAM. Since most individuals with LAM and impaired lung function are now on sirolimus, future studies may prove more difficult. Laboratory studies suggested that Imatinib mesylate (imatinib), an FDA-approved drug for leukemia, initiates LAM cell death. A pilot trial with imatinib titled "Imatinib Mesylate for the treatment of Lymphangioleiomyomatosis" - (LAMP-1) was funded by the Department of Defense in 2016, and documented (1) the safety of use of tyrosine kinase inhibitors in patients with LAM; (2) the safety of concurrent use of tyrosine kinase and mTOR inhibitors; and, (3) short term variability in vascular endothelial growth factor D (VEGF-D) - a LAM biomarker, as a response to therapies. Due to the short-term LAMP-1 trial, LAMP-2 will be a longer-term 6-month clinical study evaluating the safety and tolerability of imatinib in patients with LAM. Patients that participate in the trial will come in for 5 office visits and check-up phone calls every 2 weeks over the course of 6 months.

A Phase 1, Randomized, Double-blinded, Placebo Controlled, Trial Evaluating the Long-term Safety and Tolerability of Imatinib for the Treatment of Lymphangioleiomyomatosis [LAMP-2 Trial]

A Phase 1 Trial Evaluating the Long-term Safety and Tolerability of Imatinib for the Treatment of Lymphangioleiomyomatosis (LAM)

Condition
Lymphangioleiomyomatosis (LAM)
Intervention / Treatment

-

Contacts and Locations

New York

Columbia University Irving Medical Center, New York, New York, United States, 10032

Charleston

Medical University of South Carolina, Charleston, South Carolina, United States, 29425

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Women 18 through 64 years of age (inclusive)
  • * Pulmonary Function Test (PFT) with following criteria:
  • 1. DLCO \>20% predicted and FVC \<90% OR
  • 2. Post bronchodilator FEV1 between 30% and 90% predicted.
  • * Confirmed or possible diagnosis of LAM
  • * Willing to avoid grapefruit juice and St. John's wort while in the study
  • * Able and willing to comply with the study procedures
  • * Women who have or will undergo a transplant
  • * Women who will undergo surgery
  • * Women who are currently pregnant or plan on a pregnancy
  • * Women who are currently breast feeding or lactating
  • * Dementia or other cognitive dysfunction that, in the opinion of the investigator, would prevent the participant from consenting to the study or completing study procedures
  • * Currently taking any of the following medications:
  • * Antifungal Medications: Ketoconazole; Itraconazole ; Voriconazole.
  • * Antibiotics for bacterial infections: Clarithromycin.
  • * Analgesics to treat headaches/migraines: Dihydroergotamine; Dihydroergotamine intranasal
  • * Antiretroviral protease inhibitors used in human immunodeficiency virus (HIV) infections: Atazanavir ; Nelfinavir; Indinavir; Ritonavir; Saquinavir
  • * Anti-epileptic or seizure medications: Carbamazepine, Fosphenytoin; Oxcarbamazepine; Phenobarbital ; Phenytoin; Primidone
  • * Anti-depressant medications: Nefazodone; St. John's wort
  • * Targeted cancer drugs: Regorafenib; Venetoclax ; Cobimetinib
  • * Ivabradine (used to treat chronic heart failure); Telithromycin (used to treat community acquired pneumonia); Lomitapide (treatment of familial hypercholesterolemia); Lonafarnib (Hutchinson-Gilford progeria syndrome); conivaptan (treat low sodium levels); flibanserin (management of hypoactive sexual desire disorder (HSDD)); Naloxegol (opioid-induced constipation); Warfarin (prevent blood clots); Lurasidone (schizophrenia and bipolar depression); Eliglustat (treatment of Gaucher's disease).
  • * Non English speaking, illiterate, or other vulnerable persons will not be included among study subjects.
  • * Any condition that in the opinion of the investigator might adversely influence the study outcome.

Ages Eligible for Study

18 Years to 64 Years

Sexes Eligible for Study

FEMALE

Accepts Healthy Volunteers

No

Collaborators and Investigators

Columbia University,

Jeanine D'Armiento, MD, PhD, PRINCIPAL_INVESTIGATOR, Columbia University

Study Record Dates

2026-08